OVERALL GOAL: To test and further develop animal models of the human adult respiratory distress syndrome (ARDS) and further study mechanisms of the acute lung injury. We propose: to rigorously test a swine model developed by the principal investigator which shows acute respiratory dysfunction following hemorrhagic shock; to test the hypothesis that pharmacologic blocking of platelet aggregation will lessen or prevent the model's acute pulmonary changes; to test the hypothesis that acute hemorrhagic shock plus intra-abdominal sepsis worsens the pulmonary pathophysiology and morphology; to institute pilot studies with collaborators testing that alterations in lung defences, prostaglandin metabolism and activated serum complement are temporally related to the acute lung pathophysiology. METHODS: Young mixed breed male pigs will be anesthetized and instrumented to allow measurement of systemic and pulmonary vascular pressures, cardiac output, ventilation, in vivo lung pressure-volume curves, regional distribution of ventilation and perfusion (133 Xenon gas method), and intravascular platelet-leukocyte aggregation. Pharmacologic blocking of platelet aggregation with dipyridamole will be done randomly to test the second hypothesis. A model of intra-abdominal sepsis will be developed in the same species and combined with our proven hemorrhage model to test the third hypothesis. Pilot studies will be instituted to test that alterations in lung alveolar macrophages, activation of serum complement 3, and production of the vasoconstrictor, prostaglandins (e.g., F2 alpha), are temporally associated with the acute lung functional changes. An isolated ventilated-perfused pig lung lobe model will be developed similar to a described canine lobe model with which we have experience.